scholarly journals Tracking the Correlation Between CpG Island Methylator Phenotype and Other Molecular Features and Clinicopathological Features in Human Colorectal Cancers: A Systematic Review and Meta-Analysis

2016 ◽  
Vol 7 (3) ◽  
pp. e151 ◽  
Author(s):  
Liang Zong ◽  
Masanobu Abe ◽  
Jiafu Ji ◽  
Wei-Guo Zhu ◽  
Duonan Yu
2020 ◽  
Author(s):  
Huashi Xiao ◽  
Yingying Xu ◽  
He-chun Shen ◽  
Wanjun Liu ◽  
Siyuan Tan ◽  
...  

Abstract Backgrounds Controversy surrounding CpG island methylator phenotype (CIMP) in glioma exists with regard to its prognostic value.Methods PubMed, EMBASE, and Cochrane Library databases were searched for studies describing molecular and clinicopathological features, and overall survival of gliomas stratified by CIMP status. Associations of CIMP with outcome parameters were estimated using odds ratio (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) using a fixed or random effects model.Results A total of 12 studies involving 2386 gliomas (1051 CIMP-positive and 1335 CIMP-negative) were included. Molecular analysis showed that CIMP is more frequent in IDH1-mutated gliomas (OR 229.07; 95% CI 138.72–378.26) and 1p19q LOH gliomas (OR 5.65; 95% CI 2.66–12.01), though CIMP was not associated with EGFR mutation (OR 0.14; 95% CI 0.05–0.43) or MGMT promoter methylation (OR 3.01; 95% CI 0.79–11.48). Clinicopathological analysis showed that CIMP is more frequent in oligodendroglioma (OR 5.51; 95% CI 3.95–7.70), but less frequent in glioblastoma (OR 0.14; 95% CI 0.10–0.19). However, CIMP was not associated with anaplastic oligoastrocytomas (OR 1.57; 95% CI 1.24-2.00) or oligoastrocytoma (OR 0.79; 95% CI 0.35–1.76). We found that CIMP-positive glioma was associated with a longer overall survival (HR -0.57; 95% CI -0.97– -0.16).Conclusions A CIMP-positive glioma has better prognosis and its own molecular features (such as IDH1 and 1p19q LOH mutations) and clinicopathological features. These conditions suggest CIMP could be used as an independent prognostic marker for glioma.


2018 ◽  
Vol 11 (5) ◽  
pp. 1188-1201 ◽  
Author(s):  
Shailesh M. Advani ◽  
Pragati Advani ◽  
Stacia M. DeSantis ◽  
Derek Brown ◽  
Helena M. VonVille ◽  
...  

2016 ◽  
Vol 140 (5) ◽  
pp. 406-412 ◽  
Author(s):  
Jeong Mo Bae ◽  
Jung Ho Kim ◽  
Gyeong Hoon Kang

Context.—Colorectal cancer is a heterogeneous disease entity with 3 molecular carcinogenesis pathways and 2 morphologic multistep pathways. Right-sided colon cancers and left-sided colon and rectal cancers exhibit differences in their incidence rates according to geographic region, age, and sex. A linear tendency toward increasing frequencies of microsatellite instability–high or CpG island methylator phenotype–high cancers in subsites along the bowel from the rectum to the cecum or the ascending colon accounts for the differences in tumor phenotypes associated with these subsites. The molecular subtypes of colorectal cancers exhibit different responses to adjuvant therapy, which might be responsible for differences in subtype-specific survival. Objectives.—To review the clinicopathologic and molecular features of the molecular subtypes of colorectal cancer generated by combined CpG island methylator phenotype and microsatellite statuses, to integrate these features with the most recent findings in the context of the prognostic implications of molecular subtypes, and to emphasize the necessity of developing molecular markers that enable the identification of adenocarcinomas involving the serrated neoplasia pathway. Data Sources.—Based on the authors' own experimental data and a review of the pertinent literature. Conclusions.—Because colorectal cancers arise from 2 different morphologic multistep carcinogenesis pathways with varying contributions from 3 different molecular carcinogenesis pathways, colorectal cancer is a heterogeneous and complex disease. Thus, molecular subtyping of colorectal cancers is an important approach to characterizing their heterogeneity with respect to not only prognosis and therapeutic response but also biology and natural history.


2011 ◽  
Vol 135 (6) ◽  
pp. 698-703
Author(s):  
Gyeong Hoon Kang

Abstract Context.—In addition to chromosomal instability and microsatellite instability (MSI), a third pathway, epigenetic instability, has been implicated in progression to colorectal carcinogenesis. CpG island methylator phenotype (CIMP) refers to a subset of colorectal cancers (CRCs) that occur through the epigenetic instability pathway and that are characterized by widespread hypermethylation of promoter CpG island loci, resulting in the inactivation of several tumor suppressor genes or tumor-related genes. Colorectal cancers can be classified into 4 molecular subtypes according to their CIMP and MSI statuses: CIMP+/MSI+, CIMP+/MSI−, CIMP−/MSI+, and CIMP−/MSI−. There are differences between Western (United States and European Union) and Eastern (Korea and China) populations in the number of CRCs that are MSI+, and in the number of MSI+ CRCs that are CIMP+. Objective.—To review the clinicopathologic and molecular features of the 4 molecular subtypes of CRCs and their precursor lesions, and to emphasize geographic differences in CRCs between Eastern and Western populations. Data Sources.—This article is based on the author's own experimental data and a literature review of relevant articles indexed in PubMed (US National Library of Medicine). Conclusion.—The 4 molecular subtypes of CRC that are defined by their CIMP and MSI statuses are characterized by their own distinct clinicopathologic and molecular features and precursor lesions. In particular, the clinicopathologic features of MSI+ CRCs differ depending on the CIMP status. Further understanding of the heterogeneity in CRC molecular pathways may help to explain the diverse morphologic features of CRCs.


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